The ATTEMPT cohort: a multi-national longitudinal study of predictors, patterns and consequences of smoking cessation; introduction and evaluation of internet recruitment and data collection methods.

AIMS: The ATTEMPT study was designed to chart the natural history of smoking cessation and associated short-term health outcomes and effects on medical resource utilization among a cohort recruited across multiple countries. This paper describes the methods for recruitment and follow-up, the baseline population characteristics of the enrolled population and 1-year response rates. DESIGN: ATTEMPT is a multi-national prospective cohort study that used the internet for subject recruitment and online assessments every 3 months for 2.5 years. SETTING: Subjects were recruited via e-mail from existing internet panels [Canada (n = 208), France (n = 201), the United Kingdom (n = 200) and the United States (n = 1400]. SUBJECTS: Panel members who were aged 35-65 years, smoked at least five cigarettes per day and at initiation stated an intention to quit smoking within the next 3 months were eligible for this study. MEASUREMENTS: Measures included: attempts to quit, smoking status, smoking history, nicotine dependence and craving, methods used to quit smoking, reasons for quitting or failing to quit smoking, short-term health effects, health resource utilization, wellbeing, concern over weight gain, confidence in preventing weight gain, body weight and demographics. In addition, in-home assessments of weight were undertaken by field staff for a random sample of US participants. FINDINGS: Country-specific recruitment was completed within 17 days. The recruitment method produced a sample with characteristics broadly similar to those found in national surveys of smokers except for higher prevalence of obesity in the US and Canadian samples and higher educational level. At the end of 1 year the response rate was 52%, and there was little evidence of differential loss to follow-up by key subject characteristics. Weight reported in the survey was found to correlate highly with weight measured during in-home visits. CONCLUSION: This paper demonstrates the feasibility of enrolling and following a diverse cohort of smokers for self-reported health and behaviour measures via the internet.

Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus.

In many mendelian diseases, some mutations result in the synthesis of misfolded proteins that cannot reach a transport-competent conformation. In X-linked nephrogenic diabetes insipidus, most of the mutant vasopressin 2 (V2) receptors are trapped in the endoplasmic reticulum and degraded. They are unable to reach the plasma membrane and promote water reabsorption through the principal cells of the collecting ducts. Herein is reported two types of experiments: In vivo studies to assess clinically a short-term treatment with a nonpeptide V1a receptor antagonist (SR49059) and in vitro studies in cultured cell systems. In patients, SR49059 decreased 24- h urine volume (11.9 +/- 2.3 to 8.2 +/- 2.0 L; P = 0.005) and water intake (10.7 +/- 1.9 to 7.2 +/- 1.6 L; P < 0.05). Maximum increase in urine osmolality was observed on day 3 (98 +/- 22 to 170 +/- 52 mOsm/kg; P = 0.05). Sodium, potassium, and creatinine excretions and plasma sodium were constant throughout the study. In vitro studies indicate that the nonpeptide V1a receptor antagonist SR49059 and the V1a/V2 receptor antagonist YM087 (Conivaptan) rescued cell surface expression and function of mutant V2 receptors. Mutant V2 receptors with nonsense mutations were not affected by the treatment. Misfolded V2 receptor mutants were rescued in vitro and also in vivo by nonpeptide antagonists. This therapeutic approach could be applied to the treatment of several hereditary diseases that result from errors in protein folding and kinesis.

The effect of relcovaptan (SR 49059), an orally active vasopressin V1a receptor antagonist, on uterine contractions in preterm labor.

Relcovaptan (SR 49059) is a non-peptide, orally active vasopressin V1a receptor inhibitor. The effect on uterine contractions in 18 women with preterm labor in pregnancy weeks 32-36 was assessed in a double-blind investigation. The inclusion criterion was at least four regular uterine contractions over 30 min as measured by external tocodynamometry. Twelve patients received at random a single oral dose of 400 mg relcovaptan and six received placebo, and contractions were monitored up to 6 h thereafter. Rescue medication (beta-adrenoceptor-stimulating drug) was allowed after 2 h. Before drug administration a mean (+/- SE) of 8.2 +/- 1.4 and 9.7 +/- 1.6 contractions/30 min were recorded in the relcovaptan- and placebo-treated groups, respectively. In the former group, the frequency of uterine contractions started to decrease within the first half hour, and 1.5-2 h after dosing it was steady at 3.2 +/- 0.9 contractions/30 min. Correspondingly, after placebo, 7.8 +/- 2.2 contractions/30 min were recorded, a statistically significant difference (p = 0.017). The activity in the relcovaptan-treated women remained low, whereas in the placebo group inhibited uterine contractions were observed only in women receiving 'rescue' tocolytic treatment. It is concluded that relcovaptan inhibits preterm labor.

Hepatic involvement in hereditary hemorrhagic telangiectasia: helical computed tomography features in 24 consecutive patients.

OBJECTIVE: Among the various organs that may be affected by hereditary hemorrhagic telangiectasia (HHT), the liver can show various degrees of vascular and parenchymal involvement. The purpose of this prospective study comprising a large series of patients was to reassess the computed tomography (CT) features of hepatic involvement in HHT using helical CT. METHODS: Twenty-four consecutive patients with HHT had prospective helical CT of the liver, including noncontrast, arterial-dominant, and portal-dominant phases. The CT images were analyzed by 2 readers in consensus to determine the presence of vascular and parenchymal abnormalities. The diameter of the proper hepatic artery in these 24 patients was compared with that in 24 healthy subjects (Student t test). RESULTS: Helical CT was normal in 5 patients (21%) and abnormal in 19 patients (79%). Vascular abnormalities were found in 16 patients (67%), consisting of marked dilatation of the hepatic artery (n = 16), intrahepatic telangiectases (n = 12), arteriovenous shunting (n = 5), and arterioportal shunting (n=3). The diameter of the proper hepatic artery was greater in the patients with HHT than in control subjects (6.12 +/- 2.52 mm vs. 3.29 +/- 0.65 mm, respectively; P < 0.05). Helical CT showed nodular hyperplasia in 1 patient with vascular and parenchymal abnormalities, cavernous hemangiomas in 2 patients (1 in a patient with an enlarged hepatic artery, intrahepatic telangiectases, and arteriovenous shunting and 1 in a patient with an isolated enlarged hepatic artery), and biliary cysts in 3 patients (2 biliary cysts were present in 2 patients with an enlarged hepatic artery and intrahepatic telangiectases, and 1 biliary cyst was present without any manifestations in the third patient). CONCLUSION: Liver involvement in HHT is associated with a constellation of findings on helical CT, including significant dilatation of the proper hepatic artery, telangiectases, arteriovenous shunting, and focal liver lesions. Familiarity with these findings will result in more accurate diagnosis and allows better therapeutic options if necessary.

A useful endovascular technique for treating modular limb disconnection in a bifurcated stent-graft.

PURPOSE: To report a technique for treating a type III endoleak owing to disconnection of an iliac graft limb from a modular aortic stent-graft. TECHNIQUE: A hydrophilic guidewire is introduced via a homolateral femoral access and passed through the thrombosed iliac extension. Once the errant graft limb is recanalized, wire exchange for an extra stiff guidewire facilitates passage of an angioplasty balloon into the stent. Inflated under low pressure, the balloon is used to push the thrombosed limb retrograde into the aneurysm sac. With the aortoiliac axis restored, a new covered stent can be deployed. CONCLUSIONS: This approach is one of several that may be used to treat a type III endoleak arising from a disconnected and occluded stent-graft limb. It avoids the bleeding complications of thrombolysis and restores the aortoiliac axis so that another stent-graft may be implanted to re-exclude the aneurysm.